Ammoniated dentifrice



Patented Dec. 16, 1952 UNITED 2,622,058 AMMONI-ATED nEN'riFRIoE RobertG. Kesel, Aurora, 111., assignor to The Uni-- versity of IllinoisFoundation, a nonprofit corporation of Illinois No Drawing. ApplicationJuly 7, 1952, Serial No. 297,567

This invention relates to a dentifrice containing a non-acid salt'ofammonia in suffic'ientqu'antity substantially to inhibit lo'cabacilliand particularly to inhibit lactobacilli under naturallyoccurringconditions in the human mouth.

This application is a continuation-in-part of my copendin'g applicationNo. 52,396, filed October 1, 1948, which in turn was acontinuation-inpart of application No. 721,156, filed January 9, 1947.

Numerous dental caries studies have reported the absence of certainaciduric bacteria, particularly the absence of Lactobacillus acidophilusfrom the oral flora of individuals who have no caries. It has been shownthat saliva from individuals who have active caries contains not only alarge concentration of Lactobacillus acidophilus, but also that suchsaliva has the power to convert glucose rapidly into acid, whereassaliva from persons with no active caries does not. Procedures designedto test for caries activity have been developed based upon theseobservations.

7 It has heretofore been suggested by Grove and Grove, Dental Cosmos,October 1934, that ammonium hydroxide in very low concentrations wouldbe useful in a dentifrice for the solution of dental mucin.Investigation discloses, however, that the use of ammonium hydroxide atthe levels indicated and even at amounts several times the maximumsindicated by Grove and Grove stimulate lactobaoilli. Furthermore,because of taste and chemical action, the use of ammonium hydroxide atthe higher levels is not compatible with cultures of the saliva fromcaries active subjects develop no such inhibitory properties. It is alsoknown that the Lactobacillus acidophilus has the ability of rapidlyconverting glucose into 'acidand is in a, large measure responsible forthis action in the saliva of caries active persons.

It was discovered that inhibiting cultures produce ammonia nitrogen,while non-inhibiting cul- "tures produce ammonia'nitrogen at a muchslow-"errate and in lesser amounts. covered that the addition of basicammonium salts to a sterile broth medium-produces asub- It was furtherdisclaims. (01.167-93) stance whose inhibitory ability parallels that ofsalivary cultures having a similar ammonia nitrogen concentration. Allbasic ammonium salts can be used and are effective, but the mosteffective when used alone is ammonium carbonate. Dibasic ammoniumphosphate alone has a tendency to produce a stimulating effect on thegrowth of some undesirable -bacteria when used in concentrations of lessthan 1%. Acid am monium salts have no inhibitory characteristics.

It'was further discovered that many types of bacteria are present in thecultures of inhibitory saliva, but there is one bacterium, namely,Bacterium lactic aeroge'nes, consistently present. This organism hasbeen established by me as an ammonifier acting upon the amino'acidswhich I have found to be present in the saliva. The presence of at leasttwelve amino acids were found in human saliva and six deaminatingsystems, one of which systems is associated with B. Zactisaerogenes-namely aspartic acid which is deaminated by ammonia by theproducts of B. lactis aerogenes and particularly asparagih.Non-inhibiting cultures from saliva of caries active subjects rarelycontain the above-named bacterium. The use of the dentifrices hereindescribed Will promote the growth of this organism.

The above discoveries were made under laboratory conditions, and it wasnot known if the inhibiting properties of ammonia nitrogen could besuccessfully adapted for use in the oral cavities of humans. Adentifrice (the word dentifrice is herein used to include substances andcompositions and solutions for introduction to the oral cavity, such asmouth washes, lozenges, chewing gum, tooth cleansers-and'the like)containing a non-acid salt of ammonia will reproduce ina dentated humansimilar reductions in the count of L'actobacz'llus acidophilusencountered in'previous laboratory experiments.

To determine the effectiveness of thesepreparations on the oral flora,particularly the Lactobacillus aciolophilus content, patients wereselected from the dental clinic and student body who had a large numberof carious lesions. A Lactobacillus acidophilus count wa's made of theirsalivas and a count of 75,000 per-m1. was arbitrarily chosen asan indexof'high caries activity. Fifty-five subjects were chosen with these orhigher counts. Confirmatory tests were made on four consecutive days tomake "sure that the high counts were consistent. The group was dividedinto two sections, one a'control group, and the-other the experimentalone. The corrtrol group consisting of ten persons was to use thepreparations without the dibasic ammonium phosphate, and theexperimental group was to use the ammonium containing mouth wash andpowder.

The patients were instructed to brush their teeth thoroughly with thetooth powder and then to use about one tablespoonful of the mouth rinseand to move it vigorously over the entire mouth for two to threeminutes. This was to be done on arising and before retiring for thenight and they were also asked not to rinse the mouth with water afterusing the mouth rinse. No dietary or other instructions were given as itwas desired to learn what the unaided efiect of the ammonia might be.Patients were required to return at frequent intervals for lactobacillicounts.

The test findings are arranged in Tables I and II. The bacterial countsfor lactobacilli in the saliva of each subject before the experimentcommenced are shown in column A. These numbers are the average ofsalivary counts made on four consecutive days. The salivas werecollected and were analyzed according to the Hadley method. The numbersin column B are the average of the last two lactobacilli counts made inthe same manner from the same individuals after approximately fivemonths use of the rinse and dentifrice. The numbers in column C (TableII) are the lactobacilli counts for those of the group who continuedusing the powder and rinse for one year.

TABLE I (Control group) Efiects of five months clinical usage of monthrinse and dentifrice containing no ammonia on Zactobacilli counts (Testgroup) group. The exception was an individual who was not cooperative inusing the dentifrice and rinse. Despite the apparent huge reduction inthe counts in most of the cases, it is evident that some of the countsremained relatively high.

The study was continued for approximately one year and the number ofsubjects was expanded to 122. The results in the additional groups havebeen the same, that is, invariably there is an almost immediatereduction of lactobacilli. In some individuals the organism disappearedonly to reappear sporadically. Preliminary checks revealed no gingivalirritation from the ammonia preparations and the teeth were notably freefrom materia alba and bacterial plaques.

Because of the persistent although reduced 'l'actobacilli counts in theclinical subjects, it was decided to investigate further with ammonialiberating preparations in order to obtain a more permanent result.

Tables III to VI show the effect of a five per cent dibasic ammoniumphosphate solution on total acid production, lactic acid formation,ammonia nitrogen production, and the aciduric bacterial flora, in thesaliva of the same individual collected on a different day. The dibasicammo nium phosphate maintained the hydrogen ion concentration on thealkaline side in the presence of glucose although total titratabl-eacids were developed during the forty-eight hour incubation period toalmost the same level as occurred in the saliva without the ammoniumphosphate. Equivalent amounts of lactic acid were produced in the salivawith and without the dibasic ammonium phosphate during forty-eight hoursincubation although the ammonia did have a reducing efiect on lacticacid production as shown by the difference at the four hour period. Theanalyses for ammonia nitrogen revealed that there was a reduction inammonia in the presence of dibasic ammonium phosphate for reasons We donot know. The dibasic ammonium phosphate eliminated Lactobacillasacidophilu's from the saliva during twenty-four hours incubation,

Efiects of twelve months clinical usage of a mouth rinse and dentifricecontaining ammonia on lactobacilli counts Subject A C 698, 000 Nogrowth. 450, 000 Do. 202, 000 40,000. 410,000 12,000. 561, 000 509, 000N 0 growth. 1, 400,000 6,000.

8, 000 No growth. 1, 500, 000 15,000.

338, 000 562, 000 1,500. 150, 000 No growth 51,000 40,000. 269, 000 c000. 675, 000 No growth 375, 000 110,000. 260, 000 2,500. l, 450, 00018,000.

610, 000 No growth. 300, 000 165, 000 No growth. 470, 000 2,000. 900,000

In every instance except one the lactobacilli counts were markedlyreduced in the group using the ammonia preparations Whereas an increaseor gonly a slight decrease was observed in the control but permitted thedevelopment of coccal organisms of the streptococcus and staphylococcusvarieties. No bacteria survived the forty-eight ,hourincubation period.

Initial 4hours- 2411o11rs' 48 hours 37C. 1 37 0. 37

Tube v T.'l l.'T. T. '1. TT.T. PH .acid PH acid iacid PH acid' 7.0 01207.1 0210 7.2 7.4 7. .20 -4. 1. 50 4.0 2. 60 3. 9- 3. 00 7.7 Alk. 7,7Alk. 7.7 Alk. 7.7 Alk. 7. 75 Alk. 7.8 Alk. 7. 4 1. 0 7. 0 2. so

'Tub'e'.A =3jml. sallvai+5imL distilled water. li:ube'-'B=3-ml. saliva-Hml. glucose so1ution+4'ml. distilled we er.

Tube C=3'111l. saliva+4 ml. dib'asic' ammonium phosphate solution-I11ml. distilled water.

Tube D=3-m1..sa1iva+4 ml. dibasic ammonium phosphate solut1on'-|-20%glucose solution (1 ml).

Total-titratable acidity determined using N/100 NaOH.

TABLE W Elfiiect of 5% :dib'usz'c ammonium phosphate solution'onlacticacid production 1 4 hours 24'hours 48hours Tube Imml 37 C. 37 0.37 0.

"Rep'ortedin mg. per m1. tube'conten'ts. 'Tubescontents same as above.

TABLE V Eflect of 5% dibasic ammonium phosphate solution on ammoniumnitrogen level .Eflect of 5% di'basic. ammonium phosphate solution onaciduric flora Initial Tube .colony 24 hours.37 C. 52 6 counts 245.000226,000. 1,600,000 Uncountable. No:lactobacilli-38,000'coccal-col- Nogrowth.

onies. No 1actobacilli 11,200 coccal-col- Do.

onies.

While ammoniumphosph'at'e is preferred, other alkaline ammonium saltsmay be employed in'its place. Ammonium carbonate is a valuable salt .forthis purpose, but its instability reduces its value in. a dentifrice.

One formula for a. mouth rinseis as follows:

, Gm. or co. Dibasic'. ammonium iphosphate 50.0 Glycerin 100.0.l'jiquori amaranth- (U. 'S. '33.) 1 2.0 Soluble saccharin 1.0

Aquamenthaepiperitae, q...s 1,000.0

"in a powder than in a paste.

One formula for a tooth powder is as follows:

Inert polishing agent gm 50.0 Soluble saccharin gm 2.0 Oil of peppermintcc 4.0 Oil of cinnamon cc 2.0 Methyl salicylate gm 8.0 .Dibasic ammoniumphosphate gm 50.0 Precipitated calcium carbonate gm 884.0

It has heretofore been proposed to employ ammonium hydroxide in adentifrice for the purpose of dissolving mucin plaques from the teethbythe use of very small proportions of ammonia. Such proportions are noteffective to destroy lactobacilli and, in fact, may encourage theirrowth.

If the amount of ammonium salt used is too small, it may likewiseencourage the growth of the bacteria rather than their control.

While ammonium carbonate is apparently the most effective salt ofammonia in small concentrations, it is unstable and, therefore, it isnot particularly desirable in a dentifrice which is to be sold on themarket and may have to be stored for a considerable period of time. Itspalatability is 1ikewise not of the highest order.

Dibasic ammonium phosphate has proved to be by far the most importantand desirable salt of ammonia. This material has not heretofore beensuggested for use as a dentifrice ingredient. It may be employed as thesole ammonia producing ingredient or it may be fortified by other saltsof ammonia, so long as the dentifrice provides a non-acid integration ofthe whole.

Small amounts of dibasic ammonium phosphate in the oral environment cancause a stimulation of the growth of lactobacilli and it is,

therefore, important that the dentifrice should contain sufficient ofthe material that under normal conditions of use and dosage the bacteriawill be inhibited rather than stimulated.

It is obvious that the proportions in the dentifrice itself dependsomewhat upon the dosage of the dentifrice to be employed since thesaliva dilutes the dentifrice and this must be taken into consideration.For example, a powder is normally used in less amount than a paste andfor that reason it may be desirable to employ ahigher or at least agreater margin of safety I have found, however, that usage of 5% dibasicammonium phosphate, either in a powder or in a paste, produces the mostsatisfactory, all around results.

Under carefully controlled conditions, a powder dentifrice having 3%dibasic ammonium phosphate exerts extraordinary control of-the bacteriaand I have in some cases found an improved control at3'%' as compared to5%. The 5% levelis preferred; however, because of stability factors andmargin of safety.

Above 5%, the limiting factor is largely one of taste and palatability.Normally, any amounts above 5% may be considered as unnecessary diluentsor extenders. It is theoretically possible to employ a dentifrice withsay 10% of dibasic ammonium phosphate, using only. a half dose toproduce an ultimate solution in the mouth in the same order as thatwhich would be produced by using twice as much of the 5% material.However, up to the present this has proved impracticable because of thepalatability factor.

I have found that the lower range for ,dibasic ammonium phosphate forsafe use is above 1% A dentifricev powder including 1% dibasic ammoniumphosphate. will exert inhibitory control to use not substantially lessthan 2% bacilli control.

samples of saliva in a sterile container.

of lactobacilli in some individuals. It may be considered as borderlinecontrol at this level, and it is possible that the determining factor isthe dilution which occurs in the mouth 'of the patient.

Excellent results have been obtained in all patients treated using apowder containing 2% of dibasic ammonium phosphate allowing for ordinarydilution in the mouth. I thus prefer of the material in a dentifricepowder.

In a paste the amount of material employed may be increased and thus thedilution factor reduced. Nevertheless, even in a paste I do not preferto use substantially less than 2% of the material in order to have asafe working margin and to provide for possible loss of eifectiveness ofthe dentifrice over periods of time.

It is highly useful to employ urea with the non-acid ammonium salt.Mixtures of 2% dibasic ammonium phosphate plus 2% of urea exertexcellent control. The combination of dibasic ammonium phosphate with 3%urea as disclosed in Wach Patent No. 2,542,886 is particularlyadvantageous. Amounts of urea above approximately 10% exert an effectwhich is at least temporarily deleterious to certain functions of theoral environment, with the result that there is at least a considerablelag in lacto- However, the use of such higher proportions of urea doesnot overcome the valuable functions of the dibasic ammonium phosphateunder most conditions.

With ammonium carbonate, lower proportions may exert control and aslittle as 1% in solution is highly inhibitory. Even with this compound,however, the preferred range is not substantially less than 2% in orderto exert effective control over long periods of time, particularly sincethe salt is highly unstable and cannot be counted upon to remain at itsoriginal proportion.

A series of tests were conducted on subjects to determine theeffectiveness of water, a nonammoniated dentifrice and diiferentconcentrations of dibasic ammonium phosphate in tooth- -powders on theLactobacillus acidophilus content of the subjects saliva. The followingprocedure, devised and carried out by Dr. Joseph F. ODonnell of theUniversity of Illinois College of Dentistry, was employed.

For each test, subjects were selected from the University of IllinoisDental Clinic and student body whose lactobacilli count per 0. c. ofsaliva exceeded 10,000 and who had not used previously an ammoniateddentifrice. For each test, the

subject was permitted to rinse his mouth upon waking in the morningbefore eating his breakfast. Within from 45 to 60 minutes after eatingbreakfast, he submitted the first of five 2 c. c. The subject thenbrushed his teeth vigorously for one minute with the particular type oftoothpowder to be tested, using from 1 to 1.5 grams of the toothpowder.After spitting out the excess liquid in his mouth resulting from thebrushing, the subject then submitted the second sample of his saliva,which is the saliva sample taken immediately after brushing. The subjectthen submitted three other samples of his saliva, one taken 5 minutesafter the second sample, one taken 30 minutes after the 5 minute sample,and one taken 90 minutes after the 30 minute sample. For the series oftests in which tap water was employed instead of toothpowder. eachsubject 75 rinsed his mouth for one minute after brushing while moving20 c. c. of tap water vigorously over the entire mouth and thensubmitted the second sample of saliva.

To avoid any possible action of the medicaments in the toothpowderswhich may have been in contact with the saliva of the samples submitted,the first three samples were cultured immediately on collection.

The saliva samples were cultured and analyzed according to the FaithHadley technique. After thoroughly mixing a 2 c. 0. sample of thecollected saliva in order to break up any clumps of bacteria, 1 c. c. ofthe saliva was added to 4 c. c. of distilled, sterile water. 0.1 c. c.of this diluted saliva was then deposited on Tomato Agar having a pH of5 and spread uniformly thereover, allowed to stand for 10 minutes atroom temperature, and then incubated for 4 days at a temperature ofabout 37 C. After incubation, the lactobacilli colonies were counted.

The test findings have been arranged in Tables VII to XII. The bacterialcount in thousands for lactobacilli per 0. c. of saliva of each subjectto minutes after eating breakfast and before brushing are shown incolumns B. The lactobacilli counts in thousands immediately afterbrushing are shown in columns A; the lactobacilli counts in thousands 5minutes after brushing are shown in the columns designated 5 Min., thelactobacilli counts in thousands 30 minutes after the 5 minute samplesare shown in the columns designated 30 Min., and the lactobacilli countsin thousands minutes after the 30 minute samples are shown in columnsdesignated 90 Min.

Table VII in column 8 shows the effect of brushing and rinsing with tapwater on the lactobacilli count in the mouth.

Table VIII in column 9 shows the effect of brushing with anon-ammoniated dentifrice on the lactobaccilli count in the mouth.

Tables IX to XII in columns 9 and 10 show the effect of brushing with anammoniated toothpowder containing 1%, 2%, 3% and 5% dibasic ammoniumphosphate respectively on the lactobacilli count in the mouth.

TABLE VII Efiect of brushing and rinsing with tap water on lactobacillicounts 4 Per- Per- Per- Per- Sub ect B A c 5 30 90 out cent cent cent 1The number of lactobacilli colonies were too numerous to count.

TABLE VIII TABLE XI Enact of brushing with non-ammoniated too-th- Effectof brushing with ammoniated toothpowpowder 1 on lactobaoilli counts der1 containing 3% dibasic ammonium phos- 5 phcte Subject B A Per; 5 Per;30 Per; 90 Peg;

cen cen cen ce mm mm. mm. Per- Per- 32 B A min. min. cent 90 min. centour our.

1 Ingredients of non-ammoniated toothpowder employed: Calcium phosphategm 10.0 1 Ingredients of ammoniated toothpowder employed: solublesaccharin 4 Dibasic ammonium phosphate gm 2 91 Menthol gm. 0.4 Calciumcarbonate precipitate gm 189. 2 2o gi gtfi g g g a 53-1 1 PPPPemmtMenthol j:j:jj;;jj mjj 32 8t titii tr"""'"'"'""'"":::::::::: 132:: 21%Calcium carbonate prwpitate-- m- 8 Sodium tmri.u1ett:::::::::::::::1:11: --gm. 2. 0 1 or vsppermmt y 011 of cmnamon.00.. 0.2 Oil of Wintergreem cc 0. 6 TABLE IX Sodium lauryl sulfate gm 10 25 2 The number of Iactobaellli colonies were too numerous to count.

Effect of brushing with ammoniated toothpowder 1 containing 1 dib-asicammonium phos- TABLE XII hate p Efiecttof brushing with am-moniatedtoothmowder 1 Pep Per 30 containing 5% dibasic ammonium phosphatesublect B A 5 min. 30 min. cent min. cent difi. diff. Per 13 A 5 min. 30min. g? 90 min. cent dili.

, ingredients of ammoniated toothpowder empvl'oyed; 1 Ingredients ofammoniated toothpowder employed:

Dibasic ammonium phosphate gm 10.0 Dibasic ammonium p sp g8 Calciumphosphate 10 0 (31110111131 P ph 2 Soluble saceharin .gm 0 4 Solublesaccharm.---. 0 2 Menthol gm 0.4 Menthol 86 5 '1 Calcium carbonateprec1p1tate gm 179.2 Calcium carbonate prec p 2 4;) 011 of peppermint cc0. 4 Oil of pepper fi 2 Oil of cinnamon cc 0. 4 Oil of (311)11 6 Oil ofWintergreem co 1. 2 011 ofwmtergrern Sodium lauryl sulfate "gm" 2.0Sodium lauryl suh'afA gm 1 The number of lactobacilli colonies were toonumerous to count.

From the data in Tables VII and VIII, it is 50 readily seen thatbrushing with either tap water TABLE X or a non-ammoniated dentifricefails to efieotively reduce the laotobacilli in the saliva. In-

Efiect of brushing with flmnwmated F stead, the lactobacilli count ofpractically all of der containing dlbasw ammonium the patients increasedover a period of phate 55 minutes after brushing with either tap wateror a non-ammoniated dentifrice.

subject B A 5min 30min g; 90min 3 On the other hand, brushing in themanner No. dim previously described with a toothpowder containing thesame ingredients employed in obtaining the results in Table VIII, but inaddition having 1% dibasic ammonium phosphate, exerts some inhibitorycontrol over lactobacilli. This is evident from the data in Table IX.However, the inhibitory effect of an ammoniated toothpowder containing1% dlbasie ammonium phosphate is marginal. After the 125 minute testperiod, the lactobacilli count of only two of the subjects was reducedby more than 90% 1 Ingredients of ammoniated toothpowder employed:

Dibasic ammonium phosphate "53 of the count prior to brushing, whereasone of gg gfi ggff fg "m" 012 70 the subjects count was only reduced6.6% and Menthol H g; another only 18.8%, while the remaining two gg g gfggfg fig fffffff cc:: 0.2 subjects had a lactobacilli reduction of43.5% 011 of cinnamon 3:: 66.5%.

g f g gf gf "m' 1.0 As readily seen from Tables X to XII, excellent Thenumber of lactobacilli colonies were too numerous to count. 75 resultswere obtained using concentrations of from 2% to 5% dibasicfainmoniumphosphate in the toothpowder.

The foregoing detailed description is "given ifor 'clearness orunderstanding only, and no unportion to provide under conditions of usein the mouth a concentration in .the saliva .sumcient to inhibit.lactobacilli and beingnot substantially lessthan 2% of the composition,and a .iiavor masking ingredient.

3. A dentifrice'comprising a non-toxic, palatable carrier adapted fororal administration containing dibasic ammonium phosphate in proportionto provide under conditions of use in the mouth a concentration in thesaliva 'sufiicient to inhibit lactobacilli and being not substantiallyless than 2% of the composition, a polishing agent,zand a flavor maskingingredient.

'4.-A non-liquid dentifricecomprising .a nontoxic, palatable carrieradapted for oral administration containing dibasic ammonium phosphate.in proportion to provide under conditions of use in the mouth aconcentration in the saliva sufiicient to inhibit lactobacilli and beingnot substantially less than 2% of the composition, and a flavor maskingingredient.

5. A dentifrice comprising a non-toxic, palatable carrier adapted fororaladministration containing 'dibasic ammonium phosphate in an amountof from -2-5% of the composition and in proportion to provide underconditions of use ROBERT G. 'KESEL.

REFERENCES CITED The following referencesare of record in the file ofthis patent.

UNITED STATES PATENTS Number Name Date 1,377,780 Lane May 10, 19211,717,723 McCall June 18, 1929 1,969,340 Vogt -n Aug. 7, 1934 2,207,074Smith July 7,1940 2,452,054 Jones Oct. 26, 1948 FOREIGN PATENTS NumberCountry Date 291,565 Germany Apr. 22, 1916 342,654 Great Britain Jan.28, 1931 803,161 France June 29, 1936 OTHER REFERENCES Grove: TheBiochemical Aspect of Dental Caries? The Dental Cosmos, October 1934,pages 1029 to 1036.

The Journal of the Society of Cosmetic Chemists, Dental CariesSymposium, December 1950, volume II, Number 2, pages 57 to 87.

The Manufacturing Chemist and Manufacturing Perfumer 1), November 1949,pages 527 and 528.

The Manufacturing Chemist (2), July 1950,

page 297.

The Drug and Cosmetic Industry, September 1949, page 264.

The American Journal of Pharmacy, July 1949, page 267.

The Military Surgeon (1), May 1950, pages 352 to 354.

The Military Surgeon (2), May 1950, pages 345 to 347.

The Biochemical Journal, pages 60 to 63.

Manufacturing Chemist and Perfumer, June 1942, page 140.

Stephan et al.: Efiectiveness of Urea and of Synthetic Detergents inReducing Activity of Human Dental Caries, Proc. Soc. Exp. Biol. 8: Med.,February 1944, pages 101 to 104.

The American Perfumer, Sec. 1, .July 1949., pages 29 and 31.

The Washington Post, May 11, 1949, Dentists Told Only Fluorine AvertsDecay."

June -July 1950,

1. A DENTIFRICE COMPRISING A NON-TOXIC CARRIER ADATPED FOR ORALADMINISTRATION AND DIBASIC AMMONIUM PHOSPHATE IN PROPORTION TO PROVIDEUNDER CONDITIONS OF USE IN THE MOUTH A CONCENTRATION IN THE SALIVASUFFICIENT TO INHIBIT LACTOBACILLI AND BEING NOT SUBSTANTIALLY LESS THAN2% OF THE COMPOSITION, AND A FLAVOR MASKING INGREDIENTS.